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The Ascension is four times the size of the largest human ship, and boasts a crew of nearly 10,000. It can be seen passing the windows on the Wards while people gather around to watch. A nearby volus can be heard talking excitedly about his recent tour of the Ascension: though he was aboard for six hours, he only saw 10% of the ship, for the vessel was simply far too large to tour completely.

When the geth fleet, led by Sovereign, attacks the Citadel, the Council is evacuated to the Destiny Ascension as per standard emergency procedures. However, it fails to escape and becomes heavily damaged and thus the arrival of the Alliance Fleet is the Ascension's only hope of survival.

Commander Shepard has three choices: command the Alliance fleet to save the Destiny Ascension (at the cost of many human lives and potential reinforcements), to concentrate the attack upon Sovereign (leaving the Destiny Ascension to be destroyed by the geth fleet), or to allow the Council to die. The first option results in humanity gaining a seat on the Council. If Paragon, the second and third options results in humanity leading a new Council in cooperation with the other races. If Renegade, they result in humanity creating a new all-human council.

If the Alliance Fleet saves the Destiny Ascension, the vessel undergoes a twenty-colony victory cruise, completed in 2185. If the Destiny Ascension is destroyed at the Battle of the Citadel, a news report states that the asari have ceded the corresponding share of responsibility for Citadel defense to the turians.